A series of peptide analogs of the potent LH-RH antagonist (Ac-D-Phe,1D-p-C1-Phe,2D-Trp3,6) LH-RH will be synthesized with the goal of stabilizing this antagonist to peptidase degradation. Specifically, various peptidase-sensitive amide linkages that are part of the peptide backbone will be replaced by a ketomethylene group. Ketomethylene dipeptide analogs will be synthesized initially with the amino terminus blocked with Fmoc and the ketone blocked as a ketal. These ketomethylene dipeptide analogs will be incorporated into the desired decapeptide LH-RH antagonists by solid-phase peptide synthesis. The peptides synthesized will be tested in vitro for their ability to inhibit LH-RH induced release of LH. The peptides will also be tested in rats as antiovulatory agents. The ultimate goal of this research is to produce an antiovulatory agent that is active in animals when given orally.